Techniques to improve polyurethane membranes for implantable glucose sensors

• US 8,050,731 B2
• Filed: 11/16/2005
• Issued: 11/01/2011
• Est. Priority Date: 05/22/2002
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Tapsak, Mark A., Shults, Mark C., Rhodes, Rathbun K., McClure, Jason D.
• Primary Examiner(s): Barton; Jeffrey T
• Assistant Examiner(s): DIETERLE, JENNIFER M
• Application Number:
  US11/280,672
• Publication Number:
  US 20060086624A1
• Time in Patent Office: 2,176 Days
• Field of Search: 204/403.01, 204/403.14, 204/415, 204/403, 204/400, 525/420, 525/424, 525/440, 525/452, 525/453, 525/474, 525/296, 205/775, 205/778, 604/891.1, 604/358, 604/385.01, 600345-366, 600/372, 210/500.21, 210/500.27, 210/500.34, 428/423.1, 424/424, 424/423, 424/474
• US Class Current: 600/347
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61L 31/12 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: B01D 69/141 Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes
• CPC Class Codes: B01D 69/1411 containing dispersed material in a continuous matrix
• CPC Class Codes: B01D 71/54 Polyureas; Polyurethanes
• CPC Class Codes: B01D 71/80 Block polymers
• CPC Class Codes: B05D 3/007 After-treatment
• CPC Class Codes: B05D 5/00 Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]

Abstract

The invention provides an implantable membrane for regulating the transport of analytes therethrough that includes a matrix including a first polymer; and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400× magnification or less. In one aspect, the homogeneous membrane of the present invention has hydrophilic domains dispersed substantially throughout a hydrophobic matrix to provide an optimum balance between oxygen and glucose transport to an electrochemical glucose sensor.

Claims

1. An implantable electrochemical sensor for measuring glucose in a bodily fluid, the sensor comprising:

at least one electrode having at least a portion configured to be implanted in a host; and

a membrane disposed over the at least one electrode, the membrane comprising;

a first layer comprising a blend of (i) a hydrophobic polymer that forms a hydrophobic matrix and (ii) a hydrophobic-hydrophilic copolymer comprising hydrophilic polymer segments that traverse a thickness of the first layer, wherein the first layer is further configured to reduce a flux of glucose through the membrane, wherein the hydrophobic polymer and the hydrophobic-hydrophilic copolymer are soluble with each other, and wherein the hydrophilic polymer segments comprise hydrophilic microdomains that are substantially distributed evenly throughout the hydrophobic matrix; and

a second layer comprising an enzyme capable of reacting with glucose, wherein the second layer is more proximal to the electrode than the first layer.

2. The implantable electrochemical sensor of claim 1, wherein a hydrophobic component of the hydrophobic-hydrophilic copolymer and a hydrophobic component of the hydrophobic polymer comprise a same backbone structure.

3. The electrochemical sensor of claim 1, wherein the membrane is configured to increase a rate at which oxygen enters and passes through the membrane.

4. The electrochemical sensor of claim 1, wherein the enzyme is an oxidase.

5. The electrochemical sensor of claim 1, wherein the enzyme is glucose oxidase.

6. The electrochemical sensor of claim 1, wherein the electrode is platinum.

7. The electrochemical sensor of claim 1, wherein the sensor is configured such that a current measured by the sensor is generated by oxidation of hydrogen peroxide at the electrode.

8. The electrochemical sensor of claim 1, wherein the membrane is configured to change a ratio of oxygen to glucose from a concentration ratio in the bodily fluid of about approximately 50 to 100 parts of glucose to 1 part of oxygen to a ratio in which there is a stoichiometric excess of oxygen in the second layer.

9. The electrochemical sensor of claim 1, wherein the membrane has an oxygen-to-glucose permeability ratio of approximately 200:

1.

10. The electrochemical sensor of claim 1, wherein the first layer has a thickness of from about 5 to about 100 microns.

11. The electrochemical sensor of claim 1, wherein the hydrophilic polymer segments comprise a plurality of hydrophilic microdomains that are substantially uniform in size throughout the first layer.

12. The electrochemical sensor of claim 1, wherein the hydrophilic polymer segments are dispersed substantially throughout the hydrophobic matrix.

13. The electrochemical sensor of claim 1, wherein the hydrophilic polymer segments comprise a network of microdomains which are not photomicroscopically observable when hydrated at 400×

magnification or less.

14. The electrochemical sensor of claim 1, wherein the electrochemical sensor during use is capable of obtaining an accuracy level corresponding to having 85% of measured glucose values being within A and B regions of a standard Clarke Error Grid when the measured glucose values are compared to standard reference measurements.

15. The electrochemical sensor of claim 1, wherein the hydrophobic matrix comprises polyurethane.

16. The electrochemical sensor of claim 15, wherein the polyurethane comprises polyetherurethaneurea.

17. The electrochemical sensor of claim 1, wherein the hydrophilic polymer segments comprise polyethylene oxide.

18. The electrochemical sensor of claim 17, wherein the polyethylene oxide has an average molecular weight of from 200 to 3000.

19. The electrochemical sensor of claim 17, wherein the polyethylene oxide has an average molecular weight of from 600 to 1500.